tbuckley/cabot-search huggingface dataset:
AI in NSCLC: PET-CT &amp; histology model.
Authors: Ullas Batra, Shrinidhi Nathany, Swarsat Kaushik Nath, Joslia T Jose, Robin Sinha, Preeti P, Trapti Sharma, Sunil Pasricha, Mansi Sharma, Abhishek Bansal, Kamal Rawal
Journal: Journal of Clinical Oncology (2022)

e21044 Background: Almost 70% of cases of lung cancer are diagnosed at advanced stage, albeit with sophisticated imaging modalities available. Of these, 35% are tiny nodules that are often missed at initial radiological screening, owing to limitations of resolution of human vision.Dramatic shift in therapeutic paradigm in the management of lung cancer in the last decade has ushered an era of stratified medicine. In India, one-third population inhabits rural lands;lack of awareness for molecular medicine poses challenges to treating oncologists. AI-based cancer detection and prediction of potential oncogenic driver at diagnosis, will help alleviate patient anxiety caused due to diagnostic delays, aiding in prompt initiation of optimal therapy.Here, a comprehensive deep-CNN based diagnosis of lung adenocarcinoma (LUAD) was implemented using both PET/CT and histopathology images of 100 patients. Methods: Data collection: 143 whole-slide images were downloaded from Dartmouth Lung Cancer Histology Dataset from Biomedical Informatics Research and Data Science website and PET/CT dataset-A Large-Scale CT and PET/CT Dataset for Lung Cancer Diagnosis (Lung-PET-CT-Dx) from The Cancer Imaging Archive. This comprises 251,135 images from 355 participants across 436 studies. Creation of Deep-CNN model: Residual Neural Network - 18 was used for histopathlogic classification followed by Detectron2’s region-based deep-CNN for detection of presence of tumours in lung PET/CT images. Properties such as size, morphology, attenuation, malignancy, and spiculation were also measured. The 18-layer deep network, ResNet-18, detected the histologic patterns using whole-slide histopathology images. Results: Results for 100 patients whose PET/CT images, histopathology images, and mutational status of three genes (EGFR, ALK, ROS) were readily available. The histologic patterns of tumour cells appear to be related to the mutational status of genes. The ResNet-18 CNN could predict various histologic patterns (Acinar, Lepidic, Papillary, Micropapillary, and Solid patterns). Conclusions: CNN models can help in early diagnosis and prompt treatment of lung cancer, if fairly accurate. Larger datasets are needed to improve the same. The final validation of the model is underway and will be reported in near future.[Table: see text]
A phase 1b study of blinatumomab with the anti-programmed cell death (PD)-1 antibody AMG 404 in adults with relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL).
Authors: Cristina Papayannidis, Erika Borlenghi, David Yeung, Sigrid Machherndl-Spandl, Mar Bellido, Karamjeet Sandhu, Hansen Wong, Erik Rasmussen, Gerhard Zugmaier, Ana Markovic, Paul R. Gordon, Elias Jabbour
Journal: Journal of Clinical Oncology (2022)

e19003 Background: Preclinical data indicate that anti-PD-1 agents can facilitate activity of bispecific T-cell engager (BiTE) molecules. Here we assess the combination of the anti-CD19 BiTE molecule blinatumomab with the anti-PD-1 antibody AMG 404 in adults with R/R ALL (NCT04524455). Methods: Eligible adults with R/R ALL (Ph+ disease included) received 2-5 treatment cycles. Each cycle was 42 days, consisting of 4 weeks of cIV blinatumomab and a 2-week treatment-free interval as per label. In Cohort 1, AMG 404 was dosed IV at 240 mg every 4 weeks (Q4W); first dose was Day (D) 11 of Cycle (C) 1. Primary endpoints were dose-limiting toxicities (DLTs) and other adverse events (AEs). Results: As of 20 Dec 2021, patients (pts) from Cohort 1 (n=8) had median age of 57 (range: 24-73) y, 6/8 male, 6/8 Caucasian, 1 with extramedullary disease (duodenum), 2 with prior blinatumomab, and a median of 5 (2-15) prior treatment lines. Two pts remain on study and 2 completed the study; 4 pts discontinued the study due to death (n=3) or consent withdrawn (n=1). No DLTs were reported for the 3 evaluable pts. Of the 5 pts not evaluable for DLTs, in C1, 4 had disease progression and 1 an unrelated fatal pneumonia. Treatment-related grade (Gr) ≥3 and/or serious AEs in all 8 pts included cytokine release syndrome (CRS) (1 pt Gr 2, 1 pt Gr 1 and 3), Gr 3 increases in ALT and AST, Gr 3 fever, Gr 3-4 neutropenia, Gr 4 neutropenia/Gr 3-4 thrombocytopenia (same pt), Gr 2 sensorimotor polyneuropathy, Gr 3 hypertension, Gr 3 encephalopathy, and in 1 pt Gr 3-4 decreases in white blood cells, lymphocytes, and neutrophils. One pt developed Gr 3 SARS-COV-2 pneumonia on C2D25, resolving without clinical sequelae. C3 start was delayed by 12 days but protocol treatment resumed uneventfully. All 3 DLT-evaluable pts had a complete response (CR) or CR with partial hematologic recovery (CRh), 2/3 without measurable residual disease (MRD), within 2 cycles; the 3 rd pt had an MRD response at the end of C3. Preliminary pharmacokinetic results for the combination of blinatumomab and AMG 404 demonstrated that their exposures were consistent with those observed for each as monotherapy and did not indicate any drug-drug interactions. To date, all samples tested for anti-blinatumomab antibodies have been negative. Conclusions: In this ongoing phase 1b study, the combination of blinatumomab with AMG 404 was tolerated with a manageable safety profile. No DLTs were reported. Enrollment continues in Cohort 2 in which AMG 404 is dosed Q4W at 480 mg starting on C1D1, 48 hours prior to blinatumomab. Clinical trial information: NCT04524455. [Table: see text]
Diagnosed with advanced prostate cancer: A population-based cohort from national oncology practices.
Authors: Simon P. Kim, Kayvon Kiani, Badrinath Konety, Michael Bronsert, Nellowe Candelario, Elizabeth R Kessler, Boris Gershman, Robin Tyler, Thomas W. Flaig
Journal: Journal of Clinical Oncology (2022)

5087 Background: Clinical trials can provide access to novel systemic agents and possible improved survival for men diagnosed with regional and metastatic prostate cancer. Although clinical trials should be accessible to all patient populations, racial disparities to enrollment of clinical trials and its outcomes remain an important unknown outcome. Herein, we sought to elucidate the racial disparities in clinical trial enrollment and survival amongst advanced prostate cancer patients from a large community-based medical oncology consortium. Methods: Using CancerLinQ, we identified all patients who were diagnosed with regional (N1+) and/or metastatic (M1) prostate cancer from 2011 – 2021. Enrollment into a clinical trial and overall survival constituted the primary outcomes in this study. Multivariable logistic regression and Cox proportional hazard regression were used to identify covariates associated with each outcome. Results: Amongst the 160,888 patients with regional/metastatic prostate cancer, only 1.5% patients were enrolled in a clinical trial (n = 2,368). On multivariable analysis, patients with worse ECOG performance status were associated with lowers odds of clinical trial enrollment (p &lt; 0.001). Relative to white patients, African-American men (AAM) also had lower odds of clinical trial enrollment (OR: 0.67; p &lt; 0.001). For the entire cohort, clinical trial enrollment correlated with higher survival (HR: 1.19; p &lt; 001) and lower survival for AAM men (HR: 0.85; p &lt; 0.001) compared to white men after adjusting for other covariates. In the subgroup analysis of patients enrolled in clinical trials, AAM demonstrated similar survival to white patients (HR: 0.96, p = 0.95). Conclusions: Although African-American men with regional/metastatic prostate cancer face barriers to clinical trial enrollment, racial disparities in survival appear to resolve for patients who enroll in clinical trials. Increased attention is needed to address barriers to communication and access to clinical trials.
Phase I study of pegylated liposomal doxorubicin in combination with cyclophosphamide and vincristine in pediatric patients with relapsed/refractory sarcoma and other malignant solid tumors.
Authors: Suying Lu, Juan Wang, Junting Huang, Feifei Sun, Jia Zhu, Zijun Zhen, Hui Li, Xiaofei Sun, Yizhuo Zhang
Journal: Journal of Clinical Oncology (2022)

11519 Background: Pegylated liposomal doxorubicin (PLD) was found to have improved toxicity profile, especially with regards to reduced cardiotoxicity. The objectives of this study were to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of PLD in combination with cyclophosphamide and vincristine (PCV regimen) and describe the toxicities and response of this regimen. Methods: This was an open-label, single-center, single-arm phase I study utilizing a “3 + 3” design. The primary endpoint was the MTD of PLD, and the secondary endpoints included safety, objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Efficacy was evaluated using RECIST 1.1. PFS was defined as the time from treatment until disease progression or death. This study included cohort A and cohort B. Three dose levels were studied in cohort A, PLD 30 mg/m 2 (L1), 40 mg/m 2 (L2) or 50 mg/m 2 (L3) d1 + cyclophosphamide and mesna at 1 g/m 2 /d d1-2 + vincristine 1.5 mg/m 2 /d (≯2mg) d1 every 3 weeks. As the endpoint of the study could not be reached, we changed the dose of cyclophosphamide and mesna to 1.5 g/m 2 /d d1 in cohort B. Results: Eleven in cohort A and 34 in cohort B were enrolled, the median age was 6 years (range 1-15). Forty-three patients were eligible and evaluable for toxicity, and 35 (77.8%) patients were evaluable for response. Diagnoses were rhabdomyosarcoma (n = 29, 64.4%), Ewing's sarcoma (n = 4), and others. The median number of prior regimens was 2 (range 1-5). The most common adverse event (AE) was grade 3 or grade 4 neutropenia with a proportion of 90.9% and 65.5% in cohort A and cohort B, respectively. There was no significant difference in ORR (60% vs. 48%) and DCR (90% vs. 88%) between the two cohorts. The ORR (60% vs. 0, P = 0.019) and DCR (96.7% vs. 40%, P = 0.006) were significantly higher in Group 1 (rhabdomyosarcoma, Ewing's sarcoma, Wilm's tumor, fibrosarcoma, undifferentiated sarcoma) compared with Group 2 (neuroblastoma, osteosarcoma, embryonal sarcoma, epithelioid sarcoma, extrarenal rhabdoid tumor). The 12-month PFS of Group 1 was also better than Group 2 (79% vs. 60%, P = 0.041). Conclusions: The PCV regimen demonstrated an acceptable toxicity profile and promising clinical efficacy in pediatric patients with R/R rhabdomyosarcoma, Ewing's sarcoma, Wilm's tumor, fibrosarcoma, and undifferentiated sarcoma. Increasing the dose of cyclophosphamide did not improve the efficacy, but increased the toxicity. The RP2D for future studies is PLD 30 mg/m 2 /d for one day. Clinical trial information: NCT04213612. [Table: see text]
Detection of the presence of polymorphisms in the DPYD gene in patients with colorectal and non-colorectal digestive tumors.
Authors: Inmaculada Gallego Jimenez, Jose Luis Garcia De Veas, Clara Garcia Grove, Fernando Leopoldo Tallafigo, M. Luisa Limon
Journal: Journal of Clinical Oncology (2022)

e15530 Background: Recently the European Medicines Agency (EMA) and the Spanish Medicines Agency (AEMPS) recommend performing a phenotypic and/or genotypic test before starting treatment with fluoropyrimidines The objective of this work has been to analyze the detection of polymorphisms in the DPYD gene in order to predict toxicity to fluoropyrimidines in our study population. Methods: Prospective study of 6 months duration in which patients diagnosed with CRC and non-CRC digestive tumors with an age range of 18-99 years have been included. The technique is performed on a sample of DNA extracted from lymphocytes in peripheral blood in an EDTA tube, performing a specific fluorescent allele amplification study (AMRS), which detects point mutations, insertions or deletions of DNA. Results: During the study period, 260 patients have been included, of whom 16 mutations have been detected, all in heterozygosity. Conclusions: Various variants of DPYD have been reported to cause the absence or reduction of dihydropyrimidine dehydrogenase (DPP) activity. Through this technique we avoid the risk of serious toxicity with the administration of these drugs.[Table: see text]
Prophylactic use of metformin in patients on alpelisib treatment.
Authors: Daria Filonenko, Lyudmila Zhukova
Journal: Journal of Clinical Oncology (2022)

e13040 Background: Alpelisib-induced hyperglycemia (HG) is the most common adverse event leading to interruption, reduction or withdrawal of the treatment. HG is an on-target effect that depends on the baseline metabolic status of the patient. In SOLAR-1 90,6% patients with high-risk at baseline HG G3/G4 was reported. Prophylactic use of metformin may prevent HG in patients at risk. Methods: HR+ HER2-negative advanced breast cancer patients were stratified to low-, moderate- or high-risk groups of HG based on the algorithm published in [1] before starting alpelisib 300 mg + fulvestrant (Alp + Fulv). Moderate- and high-risk patients used prophylactic metformin at 500-1000 mg or 2000 mg BID with breakfast and dinner (Table). Metformin was started at least one-week prior Alp administration. Fasting plasma glucose (FPG) was monitored qw and bw in low- and moderate-risk patients, and daily with home glucometer in addition to bw FPG for high-risk patients. The primary endpoint of retrospective analysis was to assess the incidence of HG G3/G4 in different risk groups based on CTCAE V4.03 guidelines. Results: A cohort of 18 patients (median lines of previous treatment in advanced disease was five, all patients has received CDK4/6 inhibitors) treated with Alp+Fulv in the Loginov Moscow Clinical Scientific Centerin 2020-2021 included 7 low-, 3 moderate- and 8 high-risk patients. Any grade HG was reported in 13 out of 18 pts; no cases of HG G2 or G4 were detected. HG G3 was reported in 5 out of 18 patients including in 2 out of 3 moderate-risk patients, and in 3 out of 8 high-risk patients. Anti-HG drugs used included metformin (6/18); empagliflozin (4/18), and linagliptin (1/18); 1 patient required Alp dose reduction to 250 mg due to HG G3; none discontinued Alp due to AEs. Other AEs included rash (7/18; no grade 4; grade 3 in 4/18), and blood creatinine increase (8/18 – all grade 1-2).The median PFS on treatment with Alp+Fulv was 7 months. Conclusions: Prophylactic use of metformin in patients with high risk of hyperglycemia could markedly reduce frequency and severity of hyperglycemia on alpelisib.[Table: see text]
Effect of adjuvant chemotherapy in patients with stage III colon cancer based on the Multi-Institutional Registry of Large Bowel Cancer in Japan.
Authors: Yasuhide Yamada, Hirotoshi Kobayashi, Kengo Nagashima, Kenichi Sugihara
Journal: Journal of Clinical Oncology (2022)

3610 Background: A fluoropyrimidine plus oxaliplatin is the standard of care for stage III colon cancer but a fluoropyrimidine alone is also recommended for stage III patients in Japanese and other practice guidelines. We assessed efficacy of adjuvant fluoropyrimidine with or without oxaliplatin across a population of stage III colon patients in the Multi-Institutional Registry of Large Bowel Cancer in Japan. Methods: 7,024 of stage III colorectal cancer patients in this registry were analyzed. Endpoints were relapse-free survival (RFS) and overall survival (OS). Results: All patients received adjuvant chemotherapy between 2008 and 2011.Patient characteristics except lymph node metastases were well balanced across groups. The RFS of fluoropyrimidine with or without oxaliplatin show comparable efficacy for stage III, even for stage IIIc patients, less than 70 years old, and T4 or N2b. Median follow-up was 74.9 months in oxaliplatin combined therapy and 74.7 months in fluoropyrimidine monotherapy. The additive efficacy of oxaliplatin was not shown for RFS and OS. Conclusions: Adjuvant fluoropyrimidine monotherapy and fluoropyrimidine plus oxaliplatin show comparable efficacy benefits for the treatment of stage III of Japanese colon cancer patients; supporting fluoropyrimidine alone as standard options for the adjuvant therapy of stage III in Japan. [Table: see text]
Short-course radiotherapy combined with CAPOX and toripalimab for the total neoadjuvant therapy of locally advanced rectal cancer: Preliminary findings from a randomized, prospective, multicenter, double-arm, phase II trial (TORCH).
Authors: Yaqi Wang, Fan Xia, Lijun Shen, Juefeng Wan, Hui Zhang, Ruiyan Wu, Jingwen Wang, Yan Wang, Ye Xu, Sanjun Cai, Zhen Zhang
Journal: Journal of Clinical Oncology (2022)

e15602 Background: For patients with locally advanced rectal cancer (LARC), the standard treatment is neoadjuvant chemoradiotherapy combined with curative surgery. Total neoadjuvant therapy (TNT) has been used to increase rates of complete response and organ preservation, and achieve early control of distant metastasis. Recently, hypofractionated radiotherapy shows better synergistic effects in combination with PD-1/PD-L1 antibodies than conventional fractionated radiotherapy, as well as less impact on peripheral lymphocytes and more abscopal effects. Thus, the combination of immunotherapy and short-course radiotherapy (SCRT) based TNT is likely to further improve both tumor response and prognosis for LARC patients. Methods: TORCH is a randomized, prospective, multicentre, double-arm, phase II trial. 130 LARC (T3-4/N+M0, distance from anus ≤10cm) patients will be treated with TNT approach and assigned to the consolidation arm (A) and induction arm (B). Arm A will receive SCRT (25Gy/5Fx), followed by 6 cycles of Toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Arm B will first receive 2 cycles of ToriCAPOX, then receive SCRT, followed by 4 cycles of ToriCAPOX. Both groups will receive curative surgery or W&amp;W strategy. The primary endpoint is the rate of complete response (CR, pCR plus cCR). The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, 3-year DFS rate, 3-year OS rate, etc. The “pick the winner” method is used to investigate the better regimen. Results: Up to Jan 20th 2022, 67 patients have been recruited in the trial (arm A: 35; arm B: 32). A total of 11 patients (all MSS) have completed all neoadjuvant therapy. Most of them showed high risk factors of recurrence, including lower location (≤5cm, 10/11), deeper primary lesion invasion (cT4/MRF+, 6/11) and more positive lymph nodes (cN2, 6/11). Finally, 2 patients (both arm B) achieved cCR and received W&amp;W strategy. 9 patients received surgery and the pathological results showed 7 cases of pCR (arm A:3; arm B: 4), one near-pCR (arm A) and one non-pCR (arm A). Thus, the CR rate was amazingly high (CR rate: 81.8%, 9/11; pCR rate: 77.8%, 7/9). Even 5 patients who were evaluated as ycT3/N+/MRF+/EMVI+ before surgery was still demonstrated to be pCR after strict pathological examination. The only grade 3 AE was thrombocytopenia (4/11). And no grade 4 AE was observed. Conclusions: SCRT base TNT approach combined with Toripalimab have achieved surprisingly excellent CR rate and good tolerance in LARC patients (in our cohort), which has great clinical value in improving organ preservation. In the future, this ongoing trial will demonstrate this efficacy and compare the two arms by larger sample size. Clinical trial information: NCT04518280.
Cost-effectiveness of targeted genomic risk provision to prevent skin cancer: Results of a randomized trial.
Authors: Chi Kin Law, Amelia K Smit, Anne E. Cust, Lyndal Trevena, Pablo Fernandez Penas, Omgo E. Nieweg, Alexander M. Menzies, Sarah Wordsworth, Rachael L. Morton
Journal: Journal of Clinical Oncology (2022)

10536 Background: Many melanomas and keratinocyte cancers (KC) are preventable by reducing sun exposure and improving sun protection behaviors. Recent evidence indicates a melanoma prevention program involving personalized genomic risk information provision can reduce self-reported sunburns at 12 months in Australian adults with no history of melanoma. This was alongside genetic counselling and educational materials on skin cancer prevention and early detection. However, the economic impact of this approach was unclear. This study aimed to determine the cost-effectiveness of the program to prevent melanoma and KC. Methods: A decision-analytic Markov model was developed to simulate the lifetime cost-effectiveness of personalized genomic risk provision compared with standard prevention advice alone, from a health system perspective. We used data from the Melanoma Genomics Managing Your Risk Study Randomized Control Trial. Traditional risk was measured by a validated melanoma risk prediction model involving hair color, nevus density, history of non-melanoma skin cancer, family history of melanoma, level of sunbed sessions. Quality-adjusted life years (QALY) gained was the primary outcome measure used to estimate an incremental cost-effectiveness ratio (ICER). Both deterministic and probabilistic sensitivity analyses (PSA) were undertaken. Results: The cost of the genomic testing and risk counselling program was AUD$189 (USD$132) per participant. Genomic risk provision targeting high-traditional risk individuals was the most cost-effective lifetime strategy with an ICER of AUD$23,033 (USD$16,059) per QALY gained and an 80% probability of being cost-effective at a willingness-to-pay threshold of AUD$50,000, compared with standard preventive advice (Table). When genomic risk provision was extended to low-traditional risk groups the ICER was $43,746 (USD30,500) per QALY gained with a 45% probability of being cost-effective. Conclusions: Genomic risk provision targeted to individuals at high-traditional risk of melanoma is a cost-effective strategy for the prevention of melanoma and KCs. Long-term sustainability of the program’s effect should be examined in future research. Clinical trial information: ACTRN12617000691347. [Table: see text]